KEY TAKEAWAYS
- The TOURMALINE-MM4 Phase III trial (NCT02312258) aimed to evaluate the efficacy and safety of the oral proteasome inhibitor ixazomib as maintenance therapy in patients with NDMM who were not eligible for ASCT.
- The trial was a double-blind, placebo-controlled study. Patients were randomly assigned to receive either ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance therapy for 24 months.
- The primary measure of success was PFS from the time of allocation. The study demonstrated that ixazomib significantly extended PFS compared to the placebo. Patients with a complete or excellent partial response after induction therapy benefited enormously from ixazomib maintenance therapy.
- The study concluded that Ixazomib maintenance therapy effectively extended PFS in patients with NDMM who were not eligible for ASCT.
Maintenance therapy extends progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) who don’t get an autologous stem cell transplant (ASCT). However, immunomodulatory agents have been the only therapy used most of the time. Researchers need other choices that work well with the induction regimen and have low toxicity. The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study gave the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months to patients with NDMM who were not getting ASCT and who had at least a partial response after 6-12 months of standard induction therapy. PFS from the time of allocation was the primary measure of success.
Patients were given either ixazomib (n = 425) or a sugar pill (n = 281) at random. TOURMALINE-MM4 met its main goal because ixazomib lowered the chance of progression or death by 34.1% compared to placebo (median progression-free survival [PFS] since randomization: 17.4 vs. 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months. Patients with a complete or excellent partial response after induction were greatly helped by ixazomib (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib instead of placebo, 36.6% instead of 23.2% of patients had treatment-emergent side effects (TEAEs) of grade 3 or higher, and 12.9% instead of 8.0% stopped treatment because of TEAEs. Common TEAEs for any quality were feeling sick (26.8% v 8.0%), throwing up (24.2% v 4.3%), and having diarrhea (23.2% v 12.3%).. There was no rise in the number of new primary cancers (5.2% v 6.2%), and the number of deaths in the study was 2.6% vs. 2.2%. The study revealed that Ixazomib maintenance demonstrates prolonged PFS and favorable safety profile in non-transplant eligible newly diagnosed multiple myeloma patients, representing a significant therapeutic advancement.
Source: https://pubmed.ncbi.nlm.nih.gov/33021870/
Clinical Trial: http://clinicaltrials.gov/show/NCT02312258
Dimopoulos MA, Špička I, Quach H, Oriol A, Hájek R, Garg M, Beksac M, Bringhen S, Katodritou E, Chng WJ, Leleu X, Iida S, Mateos MV, Morgan G, Vorog A, Labotka R, Wang B, Palumbo A, Lonial S; TOURMALINE-MM4 study group. Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial. J Clin Oncol. 2020 Dec 1;38(34):4030-4041. doi: 10.1200/JCO.20.02060. Epub 2020 Oct 6. Erratum in: J Clin Oncol. 2022 Mar 10;40(8):919. PMID: 33021870; PMCID: PMC7768338.
